Lecture 4: Dry Powder Inhaler Flashcards
Inhalation dosage forms
-local and systemic
Local application of inhalation dosage forms
-high local concentration
-fast action
-lower systemic side effects
-asthma, COPD, lung infection
systemic application of inhalation dosage form
-rapid absorption
-fewer drug-metabolizing enzymes
fluticasone
-less than 1% bioavailability in oral form bc of first-pass effect
-plasma binding is more than 99% (less than 1% of drug available)
-systemic adminstation = side effects (hypercorticism)
Inhaled fluticasone
-absolute bioavailability (~10%)
-safe for children under 1
Aystemic application of inhaled medicines
-300-500 million alveoli in lungs
-huge surface area of lungs
Alveoli
-surrounded by lung capillaries
-thin walls for gas exchange (good for absorption)
-nonciliated
Respiratory tract regions
-extrathoracic (head and neck)
-upper bronchial region (trachea and bronchi)
-lower bronchial region (braonchioles)
-alveolar region
Bronchi
-large ciliated airways
bronchioles
-small ciliated airways
Particle deposition mechanisms
-diffusional transport
-inertial transport
-gravitational transport
diffusional transport
-ultrafine particles
-alveoli
-tend to be exhaled without depositing
-alveolar region
Gravitational transport
-sedimentation
-slightly bigger particles than diffusional
-increase with diameter and density
-bronchial and alveolar region
Inertial transport
-impaction
-driven by momentum
-increase with particle velocity, diameter, density
-extrathoracic region
Sedimentation increases with:
-density
-acceleration due to gravity
-diameter
-slip correction factors
Sedimentation decreases with:
-shape factors
-viscosity
sedimentation equation
-terminal settling velocity
Aerodynamic diameter (Dae)
-diameter of particle with unit mass density of 1g/cm3 that would settle at the same velocity as particle of interest
-EQUATION SLIDE 10
=(density)^0.5 x Dgeo
Particles with aerodynamic diameter > 5 um
-deposit in upper airways
-due to inertial impaction
particles with aerodynamic diameter 1-5 um
-deposit in lower airways
particles with aerodynamic diameter <1 um
-exhaled
Defense mechanisms of the upper airways (head airways)
-filtering mechanisms in nasal cavity
-trap and eliminate large particles
=sneezing and coughing
Defense mechanisms of conducting airways (lung airways)
-mucocilliary escalator
-IgA
Defense mechanisms of alveoli
-alveolar macrophages
-immunologic mechanisms: T and B lymphocytes; IgG
Types of aerosols: liquid droplets
-pressurized meter-dose inhalers (pMDIs)
-nebulizers
types of aerosols: dry particles
-dry powder inhalers (DPIs)
Propellant-driven (pressurized) metered-dose inhalers (pMDI)
-small volume of pressurized drug dispersion is isolated in a metering chamber
-released through spray orifice
-drug propelled from container, forming spray droplets after equilibriating with atmospheric pressure
pMDI pros/cons
-need good inhalation technique
-lung deposition efficiency is typically low: 5-20%
-high droplet velocity leads to extensive deposition of drug in oral areas (80%)
-drug/solvent compatibility issues with propellant
-only suitable for low-dose medications
-less expensive
components of pMDI
-drug
-propellant (CFC or HFA)
-cosolvent (ethanol)
-surfactant (sorbitan trioleate, oleic acid, lecithin)
Nebulizers
-generate droplets of drug dispersion using ENERGY from compressed air or piezoelectric ceramics
-delivered via INSPIRATORY flow
-suitable for treatment of young and elederly patients and emergency treatment
Jet nebulizers
-more time consuming than pMDIs
-require hygienic maintenance of equipment
-bulky
-low efficiency (10-15% of drug deposited)
New nebulizers
-smaller than traditional jet nebulizers
-higher delivery efficiency
-lower residues
-vibration mesh nebulizer and soft mist inhaler
Dry powder inhalers (DPI)
-dry particles in inhaler device
-aerosol of dry powder created by airflow carries particles to lungs
-deposited dose 5-40% based on formulation, device, and airflow
DPI uses
-asthma, COPD, lung infections
-insulin
Breath-actuated passive devices (passive DPI)
-powder aerosols generated by patients’ inspiratory airflow
-performance of a device could be highly variable among patients
-passive
Power-assisted active devices (active DPI)
-mechanical or electrical energy generates powder aerosols
-less dependent on patient’s inspiration capability
-active
single unit-dose DPI
-smaller inhaler
-simple design
multiple unit-dose
-convenient for frequent use
-inhaler larger
-design is complex
Particle production
-mechanical milling
-spray drying
jet milling (mechanical milling)
-apply mechanical forces to break up particles
-particles are typically cohesive with high surface energy and high electrostatic charge
-POOR flowability and POOR aerosolization performance
Spray drying
-drug dissolved into solvent
-atomized into small droplets
-dried by hot airflow through solvent evaporation
Particle interaction
-van der waals
-electrostatic (significant in dry conditions)
-capillary forces (signififcant for hygroscopic particles at high humidity
-mechanical interlocking
carrier-based DPI formulations
-act as filler for low-dose drugs
-improve flowability
Particle deposition is influenced by
-particle geometric diameter
-density
-morphology
-surface energy
-electrostatic charge
-hygroscopicity
Aerosol performance depends on carrier properties:
-particle geometric diameter
-morphology
-surface energy
-electrostatic charge
-drug to carrier ratio
-addition of additives
